Distinctive pathological structures are present in the neurons of the brains of patients suffering from neurodegenerative diseases such as Alzheimer's disease or Parkinson's disease. The pathological structures of Alzheimer's disease are termed neurofibrillary tangles and those of Parkinson's disease are termed Lewy bodies. Both types of pathological structures are composed of abnormal fibrils or filamentous deposits of proteins. Tau, one of the microtubule binding proteins, and α-synuclein have been identified as major constituents of neurofibrillary tangles and Lewy bodies, respectively. In particular, genetic analysis of familial cases of Parkinson's disease has demonstrated that the gene coding for α-synuclein is one of the responsible genes for Parkinson's disease. The observation that the number of abnormal inclusions and their regional distribution correlate with clinical symptoms in these neurodegenerative diseases has led to the postulation of a mechanism in which such abnormal structures causes cellular dysfunction and finally neuronal cell death. However this mechanism is yet to be proved by experiment.
Thus the intracellular accumulation of Tau and α-synuclein is thought to be closely related to the pathogenesis of neurodegenerative diseases. In order to prove this hypothesis, a number of researches have been performed around the world into developing a cellular model or experimental animal model to investigate the intracellular accumulation of these proteins. However at present, there have been few reports of models producing the characteristics, or characteristics similar to, the structures actually seen in the brains of patients.
Molecular reactions in which usually water-soluble proteins undergo polymerization to form insoluble aggregates or fibrils can be divided into two processes, the formation of a nucleus and processes involving fibril elongation around a nucleus. A nucleation-dependent protein polymerization model has become accepted in which the rate limiting step is the formation of the nucleus (Jarrett J T & Lansbury P T Jr, Cell 73: 1055-1058, 1993). It has been suggested to apply these processes to reactions related to fibril formation and aggregations of protein accumulating in the cell. Encouraging experimental results have been obtained in the laboratory. However methods for efficiently introducing a polymerization nucleus into a cell without causing cellular damage remain elusive and actual application to living cells or experimental animals has proven extremely difficult.